1. Field of the Invention
The present invention relates to peptides having insulin like growth factor-1 (IGF-1) and theirs uses.
2. Description of the Related Art
Insulin like growth factor-1 (IGF-1) with a molecular weight of 7,649 Da consisting of 70 amino acids is generated by human growth hormone in the liver and then secreted in blood. Its amino acid composition shows about 43% similarity to A chain of insulin. IGF-1 exhibiting similar actions to insulin is capable of binding to insulin receptor as well as its receptor, and promoting cell proliferation. IGF-1 is usually called somatomedin C due to its growth mediation activity.
It has been reported that the IGF-1 receptor is present in various tissues such as adipose tissue, lymphocyte, bond and placental membrane as well as hepatocyte. IGF-1 receptor has been revealed to have other signaling pathway than insulin receptor. The binding of IGF-1 to its receptor results in promoting somatic cell division through second messengers. IGF-1 secreted into blood from the liver is circulated as the complex form with binding protein (inactivated form). IGF-1 is separated from its binding protein in response to physiological changes or some nutrient conditions and then binds to receptors on somatic cell to stimulate cells.
IGF-1 serves to promote growth of almost all types of cells in vivo and to inhibit synthesis of glucagon in carbohydrate metabolism, resulting in the enhancement of glucose absorption into cells. Due to its similar actions to insulin, it has been focused as promising therapeutics for Laron dwarfism and insulin dependent or independent diabetes. In addition, IGF-1 having immunmodulatory activity has been researched to provide therapeutics to increase immune response of post-surgery patients and to modulate hypersensitivity reactions induced by sepsis. In particular, IGF-1 facilitates synthesis of proteoglycan in chondrocytes and serves as promising therapeutics for degenerative arthritis caused by degradation of proteoglycan in cartilage to destruct cartilage. Therefore, IGF-1 has been highlighted as a biomolecule applicable to immunmodulation and the treatment of diabetes, dwarfism, degenerative arthritis and amyotrophic lateral sclerosis.
IGF-1 has three disulfide bonds (amino acid 6-48, 18-61 and 47-52) in its backbone which is essential to its inherent activities, comprising B (1-29), C (30-41), A (42-62) and D (63-70) domains. Of them, B and A domains have been reported as a binding domain to its receptor and C and D domains have been suggested to assist a specific binding of B and A domains to IGF-1 receptor. The deletion or mutation of C and D domains permits the binding affinity of IGF-1 to be altered in which IGF-1 variants bind preferentially to insulin receptor rather than IGF-1 receptor.
For mass production of IGF-1, many researchers have made intensive researches on production of the recombinant protein using E. coli expression systems. However, these preparations are encountered to need of time- and cost-consuming refolding process and of complex purification process to remove E. coli-originated contaminants. To be free from such shortcomings, IGF-1 mimicking peptides have been prepared by solid phase synthesis methods. For instance, U.S. Pat. No. 5,473,054 filed by Jameson et al. discloses that JB2 (corresponding to amino acid 29-38 of IGF-1) and JB1 (corresponding to amino acid 61-70) fragment have cell proliferation potential and the enantiomer of JB1, JB3 has inhibitory activity to IGF-1. WO 03/048192 filed by Teruo et al. teaches that each of the peptide fragment of IGF-1 consisting of amino acid 33-37 and substance-P derived tetrapeptide exert complementary efficacy to wound healing. In addition, Kodama et al. reports that the peptide fragment of IGF-1 consisting of amino acid 50-70 has a therapeutic effect to diabetes in mice (Autoimmunity, 37:481-487 (2004)).
Throughout this application, various patents and publications are referenced, and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.